Hepatic stellate cell activation and profibrotic kinase pathways

Hepatic stellate cell (HSC) activation is the central driver of liver fibrosis, characterized by the transformation of quiescent vitamin A-storing cells into proliferative, contractile, and fibrogenic myofibroblasts (Friedman, 2008, PMID: 18195085). This process is regulated by a complex network of profibrotic kinase pathways, including the Transforming Growth Factor-beta (TGF-beta)/SMAD pathway, Platelet-Derived Growth Factor (PDGF) signaling, and various Mitogen-Activated Protein Kinase (MAPK) cascades such as ERK, JNK, and p38 (Tsuchida & Friedman, 2017, PMID: 28588322). These pathways promote the synthesis and deposition of extracellular matrix (ECM) proteins, leading to structural remodeling of the liver and eventual cirrhosis (Bataller & Brenner, 2005, PMID: 15650009). Therapeutic strategies targeting these pathways aim to inhibit HSC activation, promote their reversion to a quiescent state, or induce apoptosis to halt or reverse fibrotic progression (Puche et al., 2013, PMID: 23543714). Key molecular targets within these pathways include TGF-beta receptors, PDGF receptors, and intracellular kinases like Apoptosis Signal-regulating Kinase 1 (ASK1) and Rho-associated protein kinase (ROCK).

Other names

HSC activationHepatic fibrogenesisProfibrotic signaling cascadesStellate cell myofibroblastic transdifferentiation

Inhibition of intracellular signaling cascades (e.g., ASK1, MAPK, PI3K/Akt) and cell-surface receptors (e.g., TGFBR, PDGFR) to suppress the phenotypic transition of hepatic stellate cells to myofibroblasts and reduce collagen production.